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Lesch-Nyhan disease is a rare, sex-linked, genetic neurodevelopmental disorder that is characterized by hyperuricemia, dystonia, cognitive impairment and recurrent self-injury. We previously found reduced brain white matter volume in patients with Lesch-Nyhan disease compared with healthy adults using voxel-based morphometry. Here, we address the structural integrity of white matter via diffusion tensor imaging. We hypothesized that white matter integrity would be decreased in men with Lesch-Nyhan disease and to a lesser extent in men with a milder variant of the disease (Lesch-Nyhan variant) relative to healthy men. After acquiring diffusion-weighted brain images from Lesch-Nyhan disease (n = 5), Lesch-Nyhan variant (n = 6) and healthy participants (n = 10), we used both tract-based spatial statistics and a regions of interest approach to analyse between-group fractional anisotropy differences. We first replicated earlier findings of reduced intracranial, grey matter and white matter volumes in patients. We then discovered marked reductions of fractional anisotropy relative to the healthy control group. The Lesch-Nyhan disease group showed more pronounced reductions in white matter integrity than the Lesch-Nyhan variant group. In addition to whole brain fractional anisotropy group differences, reductions in white matter integrity were observed in the corpus callosum, corona radiata, cingulum, internal capsule and superior longitudinal fasciculus. Moreover, the variant group had attenuated dystonia severity symptoms and cognitive deficits. These findings highlight the need to better understand the role of white matter in Lesch-Nyhan disease.
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Distonía , Síndrome de Lesch-Nyhan , Sustancia Blanca , Adulto , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Humanos , Masculino , Sustancia Blanca/diagnóstico por imagenRESUMEN
Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ. GSH in dorsal anterior cingulate cortex (dACC) was acquired as a secondary 3T 1H-MRS outcome using a MEGA-PRESS sequence. Fifty healthy controls and 46 patients with SZ were studied cross-sectionally, and analyses were adjusted for effects of confounding variables. We observed lower peripheral total GSH in SZ compared to controls in extracellular (plasma) and intracellular (lymphoblast) pools. Total GSH levels in plasma positively correlated with composite neuropsychological performance across the total population and within patients. Total plasma GSH levels were also positively correlated with the levels of Glx in the dACC across the total population, as well as within each individual group (controls, patients). Furthermore, the levels of dACC Glx and dACC GSH positively correlated with composite neuropsychological performance in the patient group. Exploring the relationship between systemic oxidative stress (in particular GSH), central glutamate, and cognition in SZ will benefit further from assessment of patients with more varied neuropsychological performance.
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Esquizofrenia , Encéfalo/diagnóstico por imagen , Cognición , Ácido Glutámico , Glutatión , Giro del Cíngulo , HumanosRESUMEN
Diffusion MRI studies consistently report group differences in white matter between individuals diagnosed with schizophrenia and healthy controls. Nevertheless, the abnormalities found at the group-level are often not observed at the individual level. Among the different approaches aiming to study white matter abnormalities at the subject level, normative modeling analysis takes a step towards subject-level predictions by identifying affected brain locations in individual subjects based on extreme deviations from a normative range. Here, we leveraged a large harmonized diffusion MRI dataset from 512 healthy controls and 601 individuals diagnosed with schizophrenia, to study whether normative modeling can improve subject-level predictions from a binary classifier. To this aim, individual deviations from a normative model of standard (fractional anisotropy) and advanced (free-water) dMRI measures, were calculated by means of age and sex-adjusted z-scores relative to control data, in 18 white matter regions. Even though larger effect sizes are found when testing for group differences in z-scores than are found with raw values (p < .001), predictions based on summary z-score measures achieved low predictive power (AUC < 0.63). Instead, we find that combining information from the different white matter tracts, while using multiple imaging measures simultaneously, improves prediction performance (the best predictor achieved AUC = 0.726). Our findings suggest that extreme deviations from a normative model are not optimal features for prediction. However, including the complete distribution of deviations across multiple imaging measures improves prediction, and could aid in subject-level classification.
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Imagen de Difusión Tensora/normas , Aprendizaje Automático , Esquizofrenia/clasificación , Esquizofrenia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Medicina de Precisión , Valor Predictivo de las Pruebas , Esquizofrenia/patología , Sustancia Blanca/patología , Adulto JovenRESUMEN
AIM: To provide insight into outcome and long-term safety and efficacy of deep brain stimulation (DBS), from the perspective of individuals with Lesch-Nyhan disease (LND) and their families. METHOD: We used patient-centered outcome measures to assess long-term outcomes of DBS for 14 individuals (mean [SD] age 10y 10mo [5y 6mo], range 5-23y, all males) with LND, after an average duration of 5y 6mo (range 11mo-10y 5mo) after surgery. We compared these results with a comprehensive review of previously published cases. RESULTS: Patients and their families reported that DBS of the globus pallidus can be effective both for motor and behavioral disturbances in LND. However, outcome measures were often not significantly changed owing to substantial variability among individuals, and were overall less positive than in previous reports based on clinician assessments. In addition, there was an unexpectedly high rate of adverse events, tempering overall enthusiasm for the procedure. INTERPRETATION: Although DBS might be an effective treatment for LND, more research is needed to understand the reasons for response variability and the unusually high rates of adverse events before DBS can be recommended for these patients. What this paper adds Individuals with Lesch-Nyhan disease and their families report variable efficacy of deep brain stimulation. Long-term outcomes are associated with a high adverse event rate.
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Estimulación Encefálica Profunda , Globo Pálido/fisiopatología , Síndrome de Lesch-Nyhan/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Síndrome de Lesch-Nyhan/fisiopatología , Masculino , Evaluación del Resultado de la Atención al Paciente , Resultado del Tratamiento , Adulto JovenRESUMEN
Lesch-Nyhan disease (LND) is a rare, X-linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age-, sex-, and race-matched healthy controls (HC). Activity levels of both enzymes differed across groups (p < 0.0001), but only Gprt distinguished patients with LND from those with LNV (p < 0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.
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Guanina/metabolismo , Hipoxantina/metabolismo , Síndrome de Lesch-Nyhan/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Fibroblastos/metabolismo , Humanos , Hipoxantina Fosforribosiltransferasa/deficiencia , Hipoxantina Fosforribosiltransferasa/metabolismo , Síndrome de Lesch-Nyhan/genética , Masculino , Fenotipo , Purinas/metabolismo , Piel/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to enhance verbal productivity, but the finding and extent of enhancement vary across studies. Few attempts to replicate positive tDCS findings have been reported, suggesting the possibility of publication bias. OBJECTIVE: We aimed to replicate the tDCS methodology and findings of Cattaneo, Pisoni, and Papagno (2011, Neuroscience 183:64-70) in a new population sample. We hypothesized that our study of anodal tDCS would improve verbal fluency production similarly to the original study. METHODS: In our single-blind, sham-controlled crossover experiment, 14 healthy young adults were randomly assigned to receive 2 mA of anodal and sham stimulation to the Broca area in counterbalanced order before completing verbal fluency tasks. RESULTS: Participants tolerated the stimulation well. Despite closely mirroring the original study methods, we saw no main effect of stimulation condition: F1,13=0.002, P=0.97, letter fluency sham mean (standard deviation)=16.8 (2.3), letter fluency anodal=17.5 (3.8), category fluency sham=25.3 (5.4), or category fluency anodal=24.7 (5.2), η≤0.01. CONCLUSIONS: While tDCS may enhance cerebral functions in general, the lack of consistency between studies suggests either that this tDCS protocol does not affect verbal fluency or, at minimum, that tDCS may be more sensitive to experimental conditions than has been thought. Our findings also highlight the need for replication studies in brain stimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT01602263).
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Área de Broca/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Conducta Verbal , Estudios Cruzados , Femenino , Lóbulo Frontal , Voluntarios Sanos , Humanos , Masculino , Reproducibilidad de los Resultados , Método Simple Ciego , Adulto JovenRESUMEN
Mutations in the HPRT1 gene, which encodes the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), cause Lesch-Nyhan disease (LND) and more mildly affected Lesch-Nyhan variants. Prior studies have suggested a strong correlation between residual hypoxanthine recycling activity and disease severity. However, the relevance of guanine recycling and compensatory changes in the de novo synthesis of purines has received little attention. In the current studies, fibroblast cultures were established for 21 healthy controls and 36 patients with a broad spectrum of disease severity related to HGprt deficiency. We assessed hypoxanthine recycling, guanine recycling, steady-state purine pools, and de novo purine synthesis. There was a strong correlation between disease severity and either hypoxanthine or guanine recycling. Intracellular purines were normal in the HGprt-deficient fibroblasts, but purine wasting was evident as increased purine metabolites excreted from the cells. The normal intracellular purines in the HGprt-deficient fibroblasts were likely due in part to a compensatory increase in purine synthesis, as demonstrated by a significant increase in purinosomes. However, the increase in purine synthesis did not appear to correlate with disease severity. These results refine our understanding of the potential sources of phenotypic heterogeneity in LND and its variants.
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Guanina/metabolismo , Hipoxantina Fosforribosiltransferasa/deficiencia , Hipoxantina Fosforribosiltransferasa/metabolismo , Hipoxantina/metabolismo , Síndrome de Lesch-Nyhan/metabolismo , Purinas/biosíntesis , Células Cultivadas , Fibroblastos , Humanos , Purinas/metabolismoRESUMEN
OBJECTIVE: Postoperative delirium, occurring days after surgery, is associated with both short- and long-term adverse events. Postanesthesia care unit (PACU) delirium, immediately after recovery from anesthesia, is associated with continued delirium in the succeeding days and adverse cognitive outcomes at discharge. Longer-term consequences are unclear. The objective was to evaluate 18-month outcomes of patients with versus without delirium in the PACU after surgery with general anesthesia. METHODS: In a prospective, observational, cohort study, 91 consecutive English-speaking patients, aged at least 70 years and capable of independently providing informed consent before surgery, were followed after admission for a surgical procedure in one teaching hospital. Patients completed cognitive testing before surgery. After recovery from general anesthesia, they were evaluated for a DSM-IV diagnosis of delirium. Participants or proxies were evaluated, at a median of 19 months after surgery (interquartile range: 18-20 months), for survival, cognitive and physical functioning, and healthcare utilization outcomes. RESULTS: All 91 patients or proxies (41 with delirium [45%]) were contacted at follow-up, with 7 deaths (8%) and 3 declining further participation (3%); 81 (96% of survivors) completed follow-up evaluations, demonstrating no significant cognitive or functional decline from baseline, with 75% of the cohort living independently in the community, and no differences in any outcomes between patients with versus without PACU delirium. CONCLUSION: In a small cohort of older patients evaluated 18 months after surgery, we could not detect an association of delirium diagnosed in the PACU with patient survival, cognitive/physical functioning, and healthcare utilization.
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Periodo de Recuperación de la Anestesia , Cognición , Delirio/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Hospitalización/estadística & datos numéricos , Hospitales de Enseñanza , Humanos , Tiempo de Internación , Modelos Lineales , Masculino , Maryland , Alta del Paciente , Estudios Prospectivos , Escalas de Valoración PsiquiátricaRESUMEN
Establishing meaningful relationships between genetic variations and clinical disease is a fundamental goal for all human genetic disorders. However, these genotype-phenotype correlations remain incompletely characterized and sometimes conflicting for many diseases. Lesch-Nyhan disease is an X-linked recessive disorder that is caused by a wide variety of mutations in the HPRT1 gene. The gene encodes hypoxanthine-guanine phosphoribosyl transferase, an enzyme involved in purine metabolism. The fine structure of enzyme has been established by crystallography studies, and its function can be measured with very precise biochemical assays. This rich knowledge of genetic alterations in the gene and their functional effect on its protein product provides a powerful model for exploring factors that influence genotype-phenotype correlations. The present study summarizes 615 known genetic mutations, their influence on the gene product, and their relationship to the clinical phenotype. In general, the results are compatible with the concept that the overall severity of the disease depends on how mutations ultimately influence enzyme activity. However, careful evaluation of exceptions to this concept point to several additional genetic and non-genetic factors that influence genotype-phenotype correlations. These factors are not unique to Lesch-Nyhan disease, and are relevant to most other genetic diseases. The disease therefore serves as a valuable model for understanding the challenges associated with establishing genotype-phenotype correlations for other disorders.
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Estudios de Asociación Genética , Hipoxantina Fosforribosiltransferasa/genética , Síndrome de Lesch-Nyhan/genética , Síndrome de Lesch-Nyhan/fisiopatología , Mutación/genética , Animales , HumanosRESUMEN
Understanding the biological underpinning of relapse could improve the outcomes of patients with psychosis. Relapse is elicited by multiple reasons/triggers, but the consequence frequently accompanies deteriorations of brain function, leading to poor prognosis. Structural brain imaging studies have recently been pioneered to address this question, but a lack of molecular investigations is a knowledge gap. Following a criterion used for recent publications by others, we defined the experiences of relapse by hospitalization(s) due to psychotic exacerbation. We hypothesized that relapse-associated molecules might be underscored from the neurometabolites whose levels have been different between overall patients with early-stage psychosis and healthy subjects in our previous report. In the present study, we observed a significant decrease in the levels of N-acetyl aspartate in the anterior cingulate cortex and thalamus in patients who experienced relapse compared to patients who did not. Altogether, decreased N-acetyl aspartate levels may indicate relapse-associated deterioration of neuronal networks in patients.
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OBJECTIVE: We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups. METHODS: We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model. The hypothesized factors included attention, psychomotor speed, verbal memory, visual memory, ideational fluency, and executive functioning. RESULTS: The six-factor model provided an excellent fit for all three groups [for community controls, root mean square error of approximation (RMSEA) <0.048 and comparative fit index (CFI) = 0.99; for adults with bipolar disorder, RMSEA = 0.071 and CFI = 0.99; and for adults with schizophrenia, RMSEA = 0.06 and CFI = 0.98]. Alternate models that combined fluency with processing speed or verbal and visual memory reduced the goodness of fit. Multi-group CFA results supported factor invariance across the three groups. CONCLUSIONS: Confirmatory factor analysis supported a single six-factor structure of cognitive functioning among patients with schizophrenia or bipolar disorder and community controls. While the three groups clearly differ in level of performance, they share a common underlying architecture of information processing abilities. These cognitive factors could provide useful targets for clinical trials of treatments that aim to enhance information processing in persons with neurological and neuropsychiatric disorders.
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Trastorno Bipolar , Cognición , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Atención , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Función Ejecutiva , Análisis Factorial , Femenino , Humanos , Entrevista Psicológica/métodos , Masculino , Memoria , Modelos Psicológicos , Pruebas Neuropsicológicas , Desempeño PsicomotorRESUMEN
Apathy commonly accompanies both traumatic brain injury (TBI) and deficit syndrome schizophrenia (DSZ), despite unclear neurological bases. The authors examined differences in cortical thickness and subcortical/cerebellar regional volumes between adult TBI survivors, patients with DSZ, and healthy-control subjects by use of 3-D magnetic resonance imaging (MRI), and correlated imaging findings with clinical ratings of apathy and selected cognitive test scores. Imaging findings revealed specific areas of volume reduction in TBI survivors and areas of cortical thinning among patients with DSZ. The severity of apathy symptoms was similar across patient groups; however, severity of apathy was only correlated with imaging findings in TBI survivors.
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Apatía , Lesiones Encefálicas/patología , Lesiones Encefálicas/psicología , Hipocampo/patología , Esquizofrenia/patología , Psicología del Esquizofrénico , Adulto , Atrofia/complicaciones , Atrofia/patología , Atrofia/psicología , Encéfalo/patología , Lesiones Encefálicas/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
BACKGROUND: Postoperative delirium in the elderly, measured days after surgery, is associated with significant negative clinical outcomes. In this study, we evaluated the prevalence and in-hospital outcomes of delirium diagnosed immediately after general anesthesia and surgery in elderly patients. METHODS: Consecutive English-speaking surgical candidates, aged 70 years or older, were prospectively enrolled during July to August 2010. After surgery, each participant was evaluated for a Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of delirium in the postanesthesia care unit (PACU) and repeatedly thereafter while hospitalized. Delirium in the PACU was evaluated for an independent association with change in cognitive function from preoperative baseline testing and discharge disposition. RESULTS: Ninety-one (58% female) patients, 78% of whom were living independently before surgery, were found to have a prevalence of delirium in the PACU of 45% (41/91); 74% (14/19) of all delirium episodes detected during subsequent hospitalization started in the PACU. Early delirium was independently associated with impaired cognition (i.e., decreased category word fluency) relative to presurgery baseline testing (adjusted difference [95% confidence interval] for change in T-score: -6.02 [-10.58 to -1.45]; P = 0.01). Patients whose delirium had resolved by postoperative day 1 showed negative outcomes that were intermediate in severity between those who were never delirious during hospitalization and those whose delirium in the PACU persisted after transfer to hospital wards (adjusted probability [95% confidence interval] of discharge to institution: 3% [0%-10%], 26% [1%-51%], 39% [0%-81%] for the 3 groups, respectively). CONCLUSIONS: Delirium in the PACU is common, but not universal. It is associated with subsequent delirium on the ward, and potentially with a decline in cognitive function and increased institutionalization at hospital discharge.
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Anestesia General/efectos adversos , Delirio/diagnóstico , Diagnóstico Precoz , Actividades Cotidianas , Cuidados Posteriores , Factores de Edad , Anciano , Anciano de 80 o más Años , Periodo de Recuperación de la Anestesia , Baltimore/epidemiología , Cognición , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Delirio/epidemiología , Delirio/psicología , Delirio/terapia , Femenino , Humanos , Institucionalización , Modelos Lineales , Modelos Logísticos , Masculino , Análisis Multivariante , Pruebas Neuropsicológicas , Alta del Paciente , Transferencia de Pacientes , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Sala de Recuperación , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: Little is known about how much effort to do well most people exert on cognitive testing. Here, we describe an experimental paradigm to manipulate and measure cognitive effort. METHOD: After baseline cognitive and performance validity testing (PVT), 38 participants were assigned to a standard (SI) or enhanced (EI) incentive condition. On retesting a week later, EI participants were told that they would receive a financial bonus whose amount depended on how much their retest performance improved over baseline. SI participants were told to do their best and promised a chance-based bonus. RESULTS: Larger improvements on retesting were assumed to reflect less effort at baseline. After calculating differences from baseline to follow-up, we compared the EI and SI groups using multivariate analysis of variance. We sought to identify predictors of lower cognitive effort at baseline by correlating change z scores with baseline PVT performance and other hypothesized markers of low cognitive effort. As hypothesized, the EI group showed larger improvements, including improvements on more cognitive tests, and were rated as and reported trying harder at retesting than the SI group. Standard PVT measures did not correlate with low baseline effort; however, resting one's head or slouching during cognitive testing signified low baseline cognitive effort. CONCLUSIONS: This study provides preliminary support for an experimental paradigm to manipulate and investigate cognitive effort, which still remains poorly understood. While PVTs can detect feigned cognitive impairment, they lack the sensitivity to detect low cognitive effort in persons who pass conventional PVT cutoffs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Disfunción Cognitiva , Humanos , Reproducibilidad de los Resultados , Disfunción Cognitiva/psicología , Pruebas Neuropsicológicas , Análisis Multivariante , MotivaciónRESUMEN
Objective: Schizophrenia is associated with impairment in multiple cognitive domains. There is a paucity of research on the effect of prolonged illness duration (≥ 15 years) on cognitive performance along multiple domains. In this pilot study, we used the Global Neuropsychological Assessment (GNA), a brief cognitive battery, to explore the patterns of cognitive impairment in recent-onset (≤ 2 years) compared to chronic schizophrenia (≥ 15 years), and correlate cognitive performance with brain morphometry in patients and healthy adults. Methods: We assessed cognitive performance in patients with recent-onset (n = 17, illness duration ≤ 2 years) and chronic schizophrenia (n = 14, duration ≥ 15 years), and healthy adults (n = 16) using the GNA and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted magnetic resonance imaging images. Results: We observed cognitive deficits affecting multiple domains in the schizophrenia samples. Selectively greater impairment of perceptual comparison speed was found in adults with chronic schizophrenia (p = 0.009, η2partial = 0.25). In the full sample (n = 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes (TFCE, FWE p < 0.01). Conclusion: Along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Anterior-medial temporal gray matter volumes especially of the left hemisphere might underlie the impairment noted in this domain in schizophrenia.
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We evaluated within-person variability across a cognitive test battery by analyzing the shape of the distribution of each individual's scores within a battery of tests. We hypothesized that most healthy adults would produce test scores that are normally distributed around their own personal battery-wide, within-person (wp) mean. Using cross-sectional data from 327 neurologically healthy adults, we computed each person's mean, standard deviation, skew, and kurtosis for 30 neuropsychological measures. Raw scores were converted to T-scores using three degrees of calibration: (a) none, (b) age, and (c) age, sex, race, education, and estimated premorbid IQ. Regardless of calibration, no participant showed abnormal within-person skew (wpskew) and only 10 (3.1%) to 16 (4.9%) showed wpkurtosis greater than 2. If replicated in other samples and measures, these findings could illuminate how healthy individuals are endowed with different cognitive abilities and provide the foundation for a new method of inference in clinical neuropsychology.
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The Global Neuropsychological Assessment (GNA) is an extremely brief battery of cognitive tasks assessing episodic memory, processing speed, working memory, verbal fluency, executive function, and mood. It can be given in under 15 minutes, has five alternate forms, and does not require an examinee to be literate. The purpose of this study was to quantify practice effects over repeated administrations and assess comparability of the GNA's five alternate forms, preparing the battery for repeated administration in research and clinical settings. Forty participants each completed all five GNA forms at weekly intervals following a Latin square design (i.e., each form was administered at every position in the sequence an equal number of times). In a cognitively intact population, practice effects of 0.56 to 1.06 SD were observed across GNA measures when comparing the first and fifth administration. Most GNA tests showed nonsignificant interform differences with cross-form means differing by 0.35 SD or less, with the exception of modest but statistically significant interform differences for the GNA Story Memory subtest across all five forms. However, post hoc analysis identified clusters of two and three Story Memory alternate forms that were equivalent.
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Función Ejecutiva , Memoria a Corto Plazo , Humanos , Pruebas Neuropsicológicas , Afecto , CogniciónRESUMEN
The Iowa Gambling Task (IGT) is a measure of decision-making, in which alternative metrics have greater construct validity than conventional metrics. No large scale study has examined the neural correlates in healthy adults. We administered the IGT and structural MRI to 124 healthy participants. We analyzed the conventional IGT metric of advantageous minus disadvantageous choices (i.e., decks C + D minus decks A + B), and three alternative metrics based on choices from decks D and A alone, and all selections from each deck. Using regression and voxel-based morphometry, we examined regional gray matter volumes as predictors of IGT performance. No neural correlates of the conventional metric emerged, and the neural correlates of individual deck selections were disparate from one another. Alternative metrics showed expected neural correlates of decision-making in prefrontal cortex, insula, thalamus, and other regions. IGT alternative metrics have neural correlates consistent with decision-making theory as those difference scores reduce heterogeneity in cognitive processes. The CD-AB metric construct failure may reflect an artificial amalgamation of processes. The D-A metric appears to more successfully combine multiple levels of representation (dorsolateral prefrontal cortex, sub-cortical, cerebellar).
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Corteza Cerebral/anatomía & histología , Toma de Decisiones/fisiología , Adulto , Anciano , Femenino , Juego de Azar/psicología , Juegos Experimentales , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , PsicometríaRESUMEN
Decreased productivity on verbal fluency tasks by persons with schizophrenia has been attributed to semantic system abnormalities. Semantic structure is often assessed using multidimensional scaling (MDS) to detect normal and aberrant semantic clustering. However, MDS has limitations that may be particularly problematic for such assessments. Here, we introduce a different clustering technique, singular value decomposition (SVD), to elucidate abnormalities of the semantic system in schizophrenia. We compared 102 treated outpatients with schizophrenia to 109 healthy adults on two category-cued word fluency tasks. Patients with schizophrenia showed semantic clustering patterns that differ markedly from those of healthy adults. However, SVD revealed more detailed and critical semantic system abnormalities than previously appreciated using MDS. Patients with schizophrenia showed less coherent semantic clustering of both low- and high-frequency category exemplars than healthy adults. These results suggest the intriguing possibility that impaired automatic activation of semantic information is a key deficit in schizophrenia.